Unlike benzodiazepines, z-drugs, and other habit-forming sleep aids, Suvorexant and Ramelteon bind to the receptors for melatonin and orexin. (Melatonin is a a sleep-promoting neurohormone produced by the pineal gland and orexin is a wake-promoting neuropeptide.) Insomniacs and sufferers of delayed sleep phase disorder will be pleased to learn that their sleep conditions can be managed more safely, sustainably and with fewer long-term risks using these recently approved drugs.

Even subtle impairments in sleep architecture deleteriously affects cognitive performance. It has recently been reported that certain sleep parameters, such as sleep spindles, are reliably linked to IQ. It is therefore not so hard to believe that artificially augmenting the depth and restorativeness of sleep may also enhance cognitive performance. You may be interested in this list of tips to improve sleep quality.

But improvement in sleep quality confers incontestable cognitive benefits. The electroencephalographic parameter delta power has come to be almost synonymous with “sleep pressure”, and a greater accumulation of sleep pressure by the end of the day results in a more robust sleep/wake cycle and therefore deeper, more restorative sleep.

Remeron (Mirtazepine) and Seroquel (Quetiapine) have been effectively used off-label to manage insomnia, but both of these drugs cause an insidious onset of weight gain, and quetiapine is widely known to be diabetogenic.

So what’s left in the pharmacological armamentarium? Does a perfectly safe magic bullet exist for insomnia?

Suvorexant is a drug with a novel pharmacologic profile that was approved by the FDA this year for the treatment of insomnia. Suvorexant highjacks endogenous orexinergic circuits by antagonizing orexin receptors to promote sleep. Orexin/hypocretin is a neuropeptide involved in the maintenance of wakefulness; narcolepsy (hypersomnolence) is thought to result from the autoimmune destruction of orexinergic neurons. Hence, suvorexant-induced orexinergic blockade promotes sleep.

It is true that Suvorexant and Rozerem are likely less effective than their benzodiazepine and tricyclic counterparts. But this difference in efficacy is more than made up for by their vastly superior safety profile, given the inherent risks of benzodiazepines and anticholingeric drugs.

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